Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes
Myeloid-derived suppressor cells (MDSC) contribute to an immunosuppressive network that drives cancer escape by disabling T cell adaptive immunity. The prevailing view is that MDSC-mediated immunosuppression is restricted to tissues where MDSC co-mingle with T cells. Here we show that splenic or, un...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/17375 |
| _version_ | 1811180399720660992 |
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| author | Amy W Ku Jason B Muhitch Colin A Powers Michael Diehl Minhyung Kim Daniel T Fisher Anand P Sharda Virginia K Clements Kieran O'Loughlin Hans Minderman Michelle N Messmer Jing Ma Joseph J Skitzki Douglas A Steeber Bruce Walcheck Suzanne Ostrand-Rosenberg Scott I Abrams Sharon S Evans |
| author_facet | Amy W Ku Jason B Muhitch Colin A Powers Michael Diehl Minhyung Kim Daniel T Fisher Anand P Sharda Virginia K Clements Kieran O'Loughlin Hans Minderman Michelle N Messmer Jing Ma Joseph J Skitzki Douglas A Steeber Bruce Walcheck Suzanne Ostrand-Rosenberg Scott I Abrams Sharon S Evans |
| author_sort | Amy W Ku |
| collection | DOAJ |
| description | Myeloid-derived suppressor cells (MDSC) contribute to an immunosuppressive network that drives cancer escape by disabling T cell adaptive immunity. The prevailing view is that MDSC-mediated immunosuppression is restricted to tissues where MDSC co-mingle with T cells. Here we show that splenic or, unexpectedly, blood-borne MDSC execute far-reaching immune suppression by reducing expression of the L-selectin lymph node (LN) homing receptor on naïve T and B cells. MDSC-induced L-selectin loss occurs through a contact-dependent, post-transcriptional mechanism that is independent of the major L-selectin sheddase, ADAM17, but results in significant elevation of circulating L-selectin in tumor-bearing mice. Even moderate deficits in L-selectin expression disrupt T cell trafficking to distant LN. Furthermore, T cells preconditioned by MDSC have diminished responses to subsequent antigen exposure, which in conjunction with reduced trafficking, severely restricts antigen-driven expansion in widely-dispersed LN. These results establish novel mechanisms for MDSC-mediated immunosuppression that have unanticipated implications for systemic cancer immunity. |
| first_indexed | 2024-04-11T09:01:30Z |
| format | Article |
| id | doaj.art-3703c01018fe4546bf5280e8e6082a72 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:01:30Z |
| publishDate | 2016-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3703c01018fe4546bf5280e8e6082a722022-12-22T04:32:45ZengeLife Sciences Publications LtdeLife2050-084X2016-12-01510.7554/eLife.17375Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodesAmy W Ku0Jason B Muhitch1Colin A Powers2Michael Diehl3Minhyung Kim4Daniel T Fisher5Anand P Sharda6Virginia K Clements7Kieran O'Loughlin8Hans Minderman9Michelle N Messmer10Jing Ma11Joseph J Skitzki12Douglas A Steeber13Bruce Walcheck14Suzanne Ostrand-Rosenberg15Scott I Abrams16Sharon S Evans17https://orcid.org/0000-0003-2958-6642Department of Immunology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Immunology, Roswell Park Cancer Institute, Buffalo, United States; Department of Urology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Immunology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Immunology, Roswell Park Cancer Institute, Buffalo, United States; Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Urology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Biological Sciences, University of Maryland Baltimore County, Baltimore, United StatesFlow and Image Cytometry, Roswell Park Cancer Institute, Buffalo, United StatesFlow and Image Cytometry, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Immunology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, United StatesDepartment of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, United StatesDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, United StatesDepartment of Biological Sciences, University of Maryland Baltimore County, Baltimore, United StatesDepartment of Immunology, Roswell Park Cancer Institute, Buffalo, United StatesDepartment of Immunology, Roswell Park Cancer Institute, Buffalo, United StatesMyeloid-derived suppressor cells (MDSC) contribute to an immunosuppressive network that drives cancer escape by disabling T cell adaptive immunity. The prevailing view is that MDSC-mediated immunosuppression is restricted to tissues where MDSC co-mingle with T cells. Here we show that splenic or, unexpectedly, blood-borne MDSC execute far-reaching immune suppression by reducing expression of the L-selectin lymph node (LN) homing receptor on naïve T and B cells. MDSC-induced L-selectin loss occurs through a contact-dependent, post-transcriptional mechanism that is independent of the major L-selectin sheddase, ADAM17, but results in significant elevation of circulating L-selectin in tumor-bearing mice. Even moderate deficits in L-selectin expression disrupt T cell trafficking to distant LN. Furthermore, T cells preconditioned by MDSC have diminished responses to subsequent antigen exposure, which in conjunction with reduced trafficking, severely restricts antigen-driven expansion in widely-dispersed LN. These results establish novel mechanisms for MDSC-mediated immunosuppression that have unanticipated implications for systemic cancer immunity.https://elifesciences.org/articles/17375myeloid-derived suppressor cellsT cell traffickinglymph nodeL-selectin |
| spellingShingle | Amy W Ku Jason B Muhitch Colin A Powers Michael Diehl Minhyung Kim Daniel T Fisher Anand P Sharda Virginia K Clements Kieran O'Loughlin Hans Minderman Michelle N Messmer Jing Ma Joseph J Skitzki Douglas A Steeber Bruce Walcheck Suzanne Ostrand-Rosenberg Scott I Abrams Sharon S Evans Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes eLife myeloid-derived suppressor cells T cell trafficking lymph node L-selectin |
| title | Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes |
| title_full | Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes |
| title_fullStr | Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes |
| title_full_unstemmed | Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes |
| title_short | Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes |
| title_sort | tumor induced mdsc act via remote control to inhibit l selectin dependent adaptive immunity in lymph nodes |
| topic | myeloid-derived suppressor cells T cell trafficking lymph node L-selectin |
| url | https://elifesciences.org/articles/17375 |
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